P1.21 Microrna Profiling as a Potential Predictive Tool of Giant Cell Tumor Evolving in High Grade Osteosarcoma: A Case Report

Giant cell tumor of bone (GCT) is a relatively uncommon tumor that, although generally benign, may rarely become malignant. We report a case of osteosarcoma arising 5 months after surgery for GCT.On September 2011, a 22-year-old girl presented with a left hip pain.Radiology revealed a proximal left femur osteolytic lesion highly suggestive for GCT as confirmed by biopsy. She underwent curettage and bone grafting. 4 months after surgery, the pain came back and the X-rays demonstrated a local relapse. A first biopsy confirmed the GCT diagnosis and the immunohistochemistry revealed a high level of bHCG positive cells (patient not pregnant). As imaging and clinical evolution suggested a malignant diagnosis, several biopsies were performed till the high grade osteosarcoma diagnosis. The patient was treated with neoadiuvant chemotherapy (MTX/DDP/ADN/ x2) and on September 2011 a hip resection (extra-articular) was performed. On February 2012 the patient died due to lung metastases.To investigate the correlation between the GCT and the subsequent osteosarcoma we compared the microRNA profiles from FFPE histological samples (Table 1).We added two other independent patients, corresponding to a primary GCT that did not develop in osteosarcoma (B) and to a primary osteosarcoma, not derived from GCT (C).PCA analysis of the microRNA signal intensity distribution revealed that osteosarcoma and GCT are independent lesions (Figure 1). Moreover, a stepwise change in microRNA expression was observed in the lesions which developed into osteosarcoma. We focused on microRNAs differentially down-regulated in osteosarcoma as compared to GCT. Interestingly, we found that most of them were endowed with tumor suppressor activity. This finding is relevant in order to identify i) microRNAs whose expression in GCT could be predictive of its development into osteosarcoma and ii) microRNAs whose expression, if restored, may revert or arrest osteosarcoma development. Sources of funding: New Idea Award; AIRC-ROC Fig. 1 PCA analysis. Fig. 1 Table 1 Histological samples Table 1 Derivation Reference Histology Origin Surgery GCT Giant cell tumor Patient A (case report patient) Biopsy GCT beta Giant cell tumor with &bgr;HCG positive cells Biopsy OST beta Osteosarcoma with &bgr;HCG positive cells Surgery OST Osteosarcoma Surgery CONTR gct Giant cell tumor Patient B Surgery CONTR ost Osteosarcoma Patient C